As women gain weight after the menopause fat is preferentially deposited in the abdominal, and particularly the intra- abdominal region. Risk of metabolic and cardiovascular disease also increases non-linearly after the menopause. The central theme of this research project is the study of the role of intra-abdominal fat (IAF) and estrogen in the regulation of whole body and regional adipose tissue lipolysis in women. Three specific aims will address the following hypotheses in postmenopausal women: 1) IAF volume is associated with resistance to insulin suppression of lipolysis in whole body and regional adipose tissue, 2) regular use of estrogen attenuates this resistance to insulin suppression of lipolysis, and 3) a reduction in IAF will enhance the antilipolytic action of insulin. The applicant, Rachael E. Van Pelt, PhD, is currently supported by an individual NRSA from NHLBI and has demonstrated a consistent focus and record of research productivity in the study of age-, exercise-, and hormone-related changes in body composition, metabolism and cardiovascular disease risk. Her career goal is to become an independent scientist and to develop an extramurally-funded research program to continue her focus in gerontologic research. The K01 Mentored Research Scientist Development Award would provide Dr. Van Pelt protected research time to obtain the additional research skills and experience necessary to achieve this goal. In addition to addressing the specific aims of the proposal, an important goal of her training is to learn the technically challenging micro dialysis and hyperinsulinemic, euglycemic clamp procedures, and to acquire further experience in basic bench work and stable isotope kinetics. During the award period Dr. Van Pelt will take courses through the Certificate Program in Clinical Science in the School of Medicine. She will also attend and participate in weekly research seminars, journal clubs and grand rounds, as well as relevant annual scientific meetings. Dr. Van Pelt's sponsor, Wendy M. Kohrt, PhD, is an established investigator and mentor in aging research and has a well-funded laboratory in the division of Geriatric Medicine at the University of Colorado Health Sciences Center. She and the department will provide Dr. Van Pelt the rich learning environment, resources, and technical guidance necessary to successfully complete her training and career development.